blood cells blood cells close-up of woman

Allogeneic Hematopoietic Stem Cell Transplant A potentially curative option that is primarily used in pediatric patients with HLA-matched donors1-3

Correcting the HBB
gene mutation
Allo-HSCT eligibility
limitations & risks
Outcomes by donor type
Outcomes by age
Screening for complications
Correcting the HBB
gene mutation
Allo-HSCT eligibility
limitations & risks
Outcomes by donor type
Outcomes by age
Screening for complications

By addressing the genetic deficiency, allo-HSCT is a potentially curative option for patients with TDT1-3

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a treatment option that could alleviate the need for regular transfusions and chelation by replacing a patient’s hematopoietic stem cells (which carry the mutated HBB gene) with donor cells that carry a functional copy of the HBB gene.

Many patients do not receive allo-HSCT due to the lack of suitable matched donor, presence of existing complications, or age1,3

Allo-HSCT is mostly limited to pediatric patients with a human leukocyte antigen (HLA) matched sibling donor (MSD).1,3 However, even with an HLA MSD, the treatment is associated with a risk of transplant-related mortality (TRM), graft rejection or failure, and severe immunological complications like graft-versus-host disease (GvHD). Other factors that increase the risk of mortality include the presence of existing complications and age.1,3,4
On average, only 25% to 30% patients have an MSD3
On average, only
25% to 30%
patients have an MSD3
Graphic showing, on average, only 25 to 30 percent of thalassemia patients have an MSD

Optimal outcomes are achieved in pediatric patients who have an HLA MSD2,4

A retrospective, non-interventional study, extracting data from the European Society for Blood and Marrow Transplantation (EBMT) hemoglobinopathy prospective registry database of 1493 patients (91% <18 years old; n=1359) with thalassemia major who underwent allo-HSCT between 2000 and 2010 estimated 2-year overall survival (OS) and thalassemia-free survival (TFS) to be 88% and 81%, respectively.4

In recipients of matched sibling donor (MSD) transplants (n=1061), the results were markedly different than other donor groups, with OS and TFS 91 ± 1% and 83 ± 1%, respectively.4

Survival for all
patients at 2 years4

88%
± 1%
OS
81%
± 1%
TFS

Overall survival and thalassemia-free survival rates 2 years post-HSCT by donor type4

Donor Type* Overall Survival Rate† Thalassemia-Free Survival Rate†
Matched Sibling Donor
(n=1061)		 0.91 ± 0.01 0.83 ± 0.01
Matched Related Donor
(n=127)		 0.88 ± 0.04 0.78 ± 0.05
Mismatched
(n=57)		 0.68 ± 0.11 0.68 ± 0.11
Unrelated Donor
(n=210)		 0.77 ± 0.03 0.77 ± 0.03
*Donor information missing in 38 cases (2.5%)
†P<0.001

Survival outcomes in pediatric patients with an HLA MSD decreased with age4

In 1060 patients who received a transplant from an MSD, the threshold age for optimal transplant outcomes was around 14 years. Survival rates for children <14 years old (2-year OS of 90%–96% and TFS of 83%–93%) were higher than those for adolescents (2-year OS of 82% and TFS of 74%) and adults (2-year OS of 80% and TFS of 76%).4
OS and TFS in patients with an HLA MSD by age group4
 SWIPE OR ROTATE
 
Age
<2 years
2 to <5 years
5 to <10 years
10 to <14 years
14 to <18 years
≥18 years
P-value (for trend) P-value (for trend)
  Overall Survival Thalassemia-Free Survival
Number of Patients Events 2-year OS Events 2-year TFS
66 3 0.95 ± 0.03 4 0.93 ± 0.03
266 13 0.94 ± 0.02 32 0.86 ± 0.03
352 33 0.90 ± 0.02 52 0.83 ± 0.02
197 8 0.96 ± 0.02 24 0.86 ± 0.03
97 14 0.82 ± 0.04 20 0.74 ± 0.05
82 16 0.80 ± 0.05 18 0.76 ± 0.05
  <0.001 <0.001

HLA = human leukocyte antigen; MSD = matched sibling donor; OS = overall survival; TFS = thalassemia-free survival.
Adapted from Baronciani D, Angelucci E, Potschger U, et al. Hematopoietic stem cell transplantation in thalassemia: a report
from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000–2010.
Bone Marrow Transplant. 2016;51(4):536-541.

HLA = human leukocyte antigen; MSD = matched sibling donor; OS = overall survival; TFS = thalassemia-free survival.
Adapted from Baronciani D, Angelucci E, Potschger U, et al. Hematopoietic stem cell transplantation in thalassemia: a report
from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000–2010.
Bone Marrow Transplant. 2016;51(4):536-541.

A separate analysis demonstrated optimal outcomes of allo-HSCT in pediatric patients with an HLA MSD5

A separate retrospective analysis of 1100 patients (97% <16 years old) with beta-thalassemia major who underwent allo-HSCT between 2000 and 2016 in China, India, and the United States also demonstrated optimal outcomes are achieved within pediatric patients with an HLA matched sibling donor.

  • For patients ≤6 years, patients aged 7 to 15 years, and patients aged 16 to 25 years, 5-year event-free survival was 86%, 80%, and 63%, respectively
  • Compared with matched sibling transplants, there was higher risk of acute and chronic GvHD after mismatched related and unrelated donor transplants

There is limited experience of allo-HSCT in adult patients, as very few centers perform allo-HSCT in patients over the age of 18 years, and transplant-related mortality has persistently remained around 25%.3

Comprehensive, long-term follow-up after allo-HSCT is recommended to screen for complications6

Disease-related outcomes and late effects of allo-HSCT include6:

  • Monitoring and management of mixed chimerism
  • Iron overload
  • Chronic GvHD
  • Immune reconstitution and susceptibility to infections
  • Screening for malignancies following exposure to transplant conditioning regimens and immunosuppression

 

The use of donor cells in allo-HSCT introduces the risk of potentially life-threatening and graft rejection.2,4,6

  • Incidence of severe acute GvHD (Grade III–IV) can range from 9% to 17%, and approximately 5% to 9% of patients develop extensive chronic GvHD2,4
  • TRM is an inherent risk for patients with TDT undergoing allo-HSCT, with a recent single-center study reporting an 11.6% rate of TRM7
  • Graft failure occurs in about 20% of patients with TDT who undergo allo-HSCT6-8
Risk of developing GvHD in 1493 patients from the European Society for Blood and Bone Marrow Transplantation registry who underwent HSCT between 2000-20104
Severe Acute GvHD
(grade III-IV)* 		9% (whole population)
7% (patients with HLA MSD)‡
Limited Chronic GvHD† 15% ± 1
Extensive Chronic GvHD† 6% ± 1
GvHD = graft-versus-host disease
*Risk within first 100 days post-HSCT
†2-year risk post-HSCT
‡P=0.001
Chronic GvHD assessment was done in 1140 patients who survived with a functioning graft for >100 days.

Actor portrayal. Not a real patient.

Take the Beta-Thalassemia
Challenge

Allogeneic hematopoietic stem cell transplant (allo-HSCT) using a matched sibling donor (MSD) is associated with improved mortality and lower risk of immunological complications like graft-versus-host disease (GvHD). Approximately what percentage of patients have an available MSD?

Actor portrayal. Not a real patient.